In a prospective service evaluation of 125 consecutive patients with obstructive sleep apnea syndrome (apnea-hypopnea index 4, or >4% oxygen desaturation index, >7.5 events/h, and symptoms of daytime ...tiredness and hypersomnolence) offered continuous positive airway pressure (CPAP), ESS was measured at baseline and follow-up (3-months post-CPAP initiation). ...few patients reported deterioration in their daytime sleepiness; hence, our data estimate the minimum clinically important improvement rather than the true MCID of the ESS. A multicentre randomised controlled trial and economic evaluation of continuous positive airway pressure for the treatment of obstructive sleep apnoea syndrome in older people: PREDICT.
Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence ...regarding its ability to improve physical activity levels.
To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate-intensity physical activity (time expending ≥3 metabolic equivalents METs) by people with COPD.
In this single-blind randomized controlled trial, participants were assigned 1:1 to receive a control intervention (PR comprising 8 wk, two supervised sessions per week) or the trial intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 wk). In the randomization process, we used minimization to balance groups for age, sex, FEV
percent predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was based on the intention-to-treat principle.
The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time expending at least 3 METs. A total of 152 participants (72% male; mean SD FEV
percent predicted, 50.5% 21.2; median first quartile, third quartile time expending ≥3 METs, 46 21, 92 min) were enrolled and assigned to the intervention (n = 76) or control (n = 76) arm. There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks (median first quartile, third quartile difference, 0.5 -1.0, 31.0 min; P = 0.87) or at the 6-month follow-up (7.0 -9, 27 min; P = 0.16).
Pedometer-directed step-count targets during an outpatient PR program did not enhance moderate-intensity physical activity levels in people with COPD. Clinical trial registered with www.clinicaltrials.gov (NCT01719822).
Summary Background & aims Bioelectrical impedance analysis (BIA) provides a simple method to assess changes in body composition. Raw BIA variables such as phase angle provide direct information on ...cellular mass and integrity, without the assumptions inherent in estimating body compartments, e.g. fat-free mass (FFM). Phase angle is a strong functional and prognostic marker in many disease states, but data in COPD are lacking. Our aims were to describe the measurement of phase angle in patients with stable COPD and determine the construct and discriminate validity of phase angle by assessing its relationship with established markers of function, disease severity and prognosis. Methods 502 outpatients with stable COPD were studied. Phase angle and FFM by BIA, quadriceps strength (QMVC), 4-m gait speed (4MGS), 5 sit-to-stand time (5STS), incremental shuttle walk (ISW), and composite prognostic indices (ADO, iBODE) were measured. Patients were stratified into normal and low phase angle and FFM index. Results Phase angle correlated positively with FFM and functional outcomes (r = 0.35–0.66, p < 0.001) and negatively with prognostic indices (r = −0.35 to −0.48, p < 0.001). In regression models, phase angle was independently associated with ISW, ADO and iBODE whereas FFM was removed. One hundred and seventy patients (33.9% 95% CI, 29.9–38.1) had a low phase angle. Phenotypic characteristics included lower QMVC, ISW, and 4MGS, higher 5STS, ADO and iBODE scores, and more exacerbations and hospital days in past year. The proportion of patients to have died was significantly higher in patients with low phase angle compared to those with normal phase angle (8.2% versus 3.6%, p = 0.02). Conclusion Phase angle relates to markers of function, disease severity and prognosis in patients with COPD. As a directly measured variable, phase angle offers more useful information than fat-free mass indices.
Interstitial lung disease and associated fibrosis occur in a proportion of individuals who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through unknown ...mechanisms. We studied individuals with severe coronavirus disease 2019 (COVID-19) after recovery from acute illness. Individuals with evidence of interstitial lung changes at 3 to 6 months after recovery had an up-regulated neutrophil-associated immune signature including increased chemokines, proteases, and markers of neutrophil extracellular traps that were detectable in the blood. Similar pathways were enriched in the upper airway with a concomitant increase in antiviral type I interferon signaling. Interaction analysis of the peripheral phosphoproteome identified enriched kinases critical for neutrophil inflammatory pathways. Evaluation of these individuals at 12 months after recovery indicated that a subset of the individuals had not yet achieved full normalization of radiological and functional changes. These data provide insight into mechanisms driving development of pulmonary sequelae during and after COVID-19 and provide a rational basis for development of targeted approaches to prevent long-term complications.
Background
Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic ...implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men.
Methods
We identified miRNAs associated with a low fat‐free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR‐675 and miR‐519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community‐dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence.
Results
Imprinted miRNAs (miR‐675 and from a cluster, C19MC which includes miR‐519a) were differentially expressed in the quadriceps of patients with a low fat‐free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR‐675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR‐519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR‐675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR‐675 represses regeneration.
Conclusions
The data suggest that increased expression of miR‐675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.
Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown.
...To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation.
816 outpatients with COPD (mean (SD) age 70 (10) years, FEV
% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex.
209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty.
Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term.
Exercise Training in COPD: FITT for Purpose? Patel, Suhani; Maddocks, Matthew; Man, William D.-C.
Chest,
July 2020, 2020-07-00, 20200701, Letnik:
158, Številka:
1
Journal Article
Summary Background Little is known about COPD patients’ compliance with physical activity monitoring and how activity relates to disease characteristics in a multi-center setting. Methods In a ...prospective study at three Northern European sites physical activity and clinical disease characteristics were measured in 134 COPD patients (GOLD-stage II–IV; BODE index 0–9) and 46 controls. Wearing time, steps per day, and the physical activity level (PAL) were measured by a multisensory armband over a period of 6 consecutive days (in total, 144h). A valid measurement period was defined as ≥22 h wearing time a day on at least 5 days. Results The median wearing time was 142 h:17 min (99%), 141 h:1min (98%), and 142 h:24 min (99%), respectively in the three centres. A valid measurement period was reached in 94%, 97%, and 94% of the patients and did not differ across sites ( P = 0.53). The amount of physical activity did not differ across sites (mean steps per day, 4725 ± 3212, P = 0.58; mean PAL, 1.45 ± 0.20, P = 0.48). Multivariate linear regression analyses revealed significant associations of FEV1 , 6-min walk distance, quadriceps strength, fibrinogen, health status, and dyspnoea with both steps per day and PAL. Previously unrecognized correlates of activity were grade of fatigue, degree of emphysema, and exacerbation rate. Conclusions The excellent compliance with wearing a physical activity monitor irrespective of study site and consistent associations with relevant disease characteristics support the use of activity monitoring as a valid outcome in multi-center studies.
Background
Cachexia is an important extra‐pulmonary manifestation of chronic obstructive pulmonary disease (COPD) presenting as unintentional weight loss and altered body composition. Previous ...studies have focused on the relative importance of body composition compared with body mass rather than the relative importance of dynamic compared with static measures. We aimed to determine the prevalence of cachexia and pre‐cachexia phenotypes in COPD and examine the associations between cachexia and its component features with all‐cause mortality.
Methods
We enrolled 1755 consecutive outpatients with stable COPD from two London centres between 2012 and 2017, stratified according to European Respiratory Society Task Force defined cachexia unintentional weight loss >5% and low fat‐free mass index (FFMI), pre‐cachexia (weight loss >5% but preserved FFMI), or no cachexia. The primary outcome was all‐cause mortality. We calculated hazard ratios (HRs) using Cox proportional hazards regression for cachexia classifications (cachexia, pre‐cachexia, and no cachexia) and component features (weight loss and FFMI) and mortality, adjusting for age, sex, body mass index, and disease‐specific prognostic markers.
Results
The prevalence of cachexia was 4.6% 95% confidence interval (CI): 3.6–5.6 and pre‐cachexia 1.6% (95% CI: 1.0–2.2). Prevalence was similar across sexes but increased with worsening Global Initiative for Chronic Obstructive Pulmonary Disease spirometric stage and Medical Research Council dyspnoea score (all P < 0.001). There were 313 (17.8%) deaths over a median (interquartile range) follow‐up duration 1089 (547–1704) days. Both cachexia HR 1.98 (95% CI: 1.31–2.99), P = 0.002 and pre‐cachexia HR 2.79 (95% CI: 1.48–5.29), P = 0.001 were associated with increased mortality. In multivariable analysis, the unintentional weight loss feature of cachexia was independently associated with mortality HR 2.16 (95% CI: 1.31–3.08), P < 0.001, whereas low FFMI was not HR 0.88 (95% CI: 0.64–1.20), P = 0.402. Sensitivity analyses using body mass index‐specific, age‐specific, and gender‐specific low FFMI values found consistent findings.
Conclusions
Despite the low prevalence of cachexia and pre‐cachexia, both confer increased mortality risk in COPD, driven by the unintentional weight loss component. Our data suggest that low FFMI without concurrent weight loss may not confer the poor prognosis as previously reported for this group. Weight loss should be regularly monitored in practice and may represent an important target in COPD management. We propose the incorporation of weight monitoring into national and international COPD guidance.
Age-related loss of muscle, sarcopenia, is recognised as a clinical syndrome with multiple contributing factors. International European Working Group on Sarcopenia in Older People (EWGSOP) criteria ...require generalised loss of muscle mass and reduced function to diagnose sarcopenia. Both are common in COPD but are usually studied in isolation and in the lower limbs.
To determine the prevalence of sarcopenia in COPD, its impact on function and health status, its relationship with quadriceps strength and its response to pulmonary rehabilitation (PR).
EWGSOP criteria were applied to 622 outpatients with stable COPD. Body composition, exercise capacity, functional performance, physical activity and health status were assessed. Using a case-control design, response to PR was determined in 43 patients with sarcopenia and a propensity score-matched non-sarcopenic group.
Prevalence of sarcopenia was 14.5% (95% CI 11.8% to 17.4%), which increased with age and Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stage, but did not differ by gender or the presence of quadriceps weakness (14.9 vs 13.8%, p=0.40). Patients with sarcopenia had reduced exercise capacity, functional performance, physical activity and health status compared with patients without sarcopenia (p<0.001), but responded similarly following PR; 12/43 patients were no longer classified as sarcopenic following PR.
Sarcopenia affects 15% of patients with stable COPD and impairs function and health status. Sarcopenia does not impact on response to PR, which can lead to a reversal of the syndrome in select patients.
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